We propose research which will evaluate the effects of experimental coronary-myocardial ischemia on the transcapillary exchange and tissue distribution of radioisotopes and the cardiac lymph clearance of fluid, proteins and enzymes. In open-chest dog preparations, the transport effects of mild, moderate and severe ischemia induced by coronary constriction will be measured by single-pass bolus-injection multiple indicator curves and the timed collection and analysis for protein and enzymes of cardiac lymph. Tracers will be allowed to enter the left anterior descending coronary artery through a cannula. Outflow samples will be collected from the coronary sinus. Ischemia will be produced by constrictuion or total occlusion of the cannula flow. Cardiac lymph will be collected through a separate cannula placed in a lymphatic vessel afferent to the cardiac lymph node. Several mathematical theories will be used to infertransport properties from these observations. Ischemic effects on transport will be compared to transport changes resulting from increased capillary pressure and infusions of three drugs which may affect capillary-tissue exchange: hyaluronidase, histamine and adenosine. The results will be used to evaluate the diagnostic importance of transport alterations in coronary disease and to suggest targets for therapeutic control of capillary permeability.